Malaria is a parasitic disease which is caused by various species of Plasmodium protozoa. Together with AIDS and TB, malaria is responsible for largest number of deaths annually. The high rate of mortality associated with malaria can be attributed to the increasing cases of resistance of Plasmodium falciparum, the most deadly of the four human infecting malarial parasites, to the contemporary antimalarial drugs. Chloroquine is one of the most inexpensive, readily available, and probably most prescribed drugs for the chemotherapy of malaria, it has been rendered ineffective in many parts of the world, due to the emergence of multidrug-resistant P. falciparum. Against this background, discovery of artemisinin as the active principle of Chinese traditional drug against malaria, Artemisia annua, is an important milestone in malaria chemotherapy. Artemisinin is active against both chloroquine sensitive and chloroquine resistant malaria.

Semisynthetic derivatives of artemisinin such as arteether, artemether and artesunic acid, are several times more potent than the parent compound.
The limited availability of artemisinin from malaria such as cerebral malaria [For reviews on artemisinin and its analogues see: (a) Klayman, D. L Science 1985, 228, 1049. (b) Bhattacharya, A. K.; Sharma, R. P. Heterocycles 1999, 51, 1681. (c) Borstnik, K.; Paik, I.; Shapiro, T. A.; Posner, G. H. Int. J Parasitol. 2002, 32, 1661. (d) Ploypradith, P. Acta Trop. 2004, 89, 329. (e) O'Neill, P. M.; Posner, G. H. J. Med. Chem. 2004, 47, 2945].natural source and recognition of endoperoxide linkage in the form of a 1,2,4-trioxane ring system as the antimalarial pharmacophore of these compounds, has led to the present efforts to develop structurally simple synthetic trioxanes as substitutes of artemisinin derivatives. Several of these synthetic 1,2,4-trioxanes have shown promising antimalarial activity [(a) Bhattacharya, A. K.; Sharma, R. P. Heterocycles 1999, 51, 1681. (b) Borstnik, K.; Paik, I.; Shapiro, T. A.; Posner, G. H. Int. J. Parasitol. 2002, 32, 1661. (c) Singh, C.; Misra, D.; Saxena, G.; Chandra, S. Bioorg. Med. Chem. Lett. 1995, 5, 1913. (d) Singh, C.; Puri, S. K. U.S. Pat. No. 6,316,493 B1, 2001. (e) Singh, C.; Malik, H.; Puri, S. K. Bioorg. Med. Chem. Lett. 2004, 14, 459. (f) Singh, C.; Gupta, N.; Puri, S. K. Bioorg. Med. Chem. 2004, 12, 5553. (g) Singh, C.; Tiwari, P.; Puri, S. K. PCT Patent application No. PCT/1N02/00093, dated Mar. 28, 2002. (h) Singh, C. Malik, H.; Puri, S. K. PCT Patent application No. PCT/1N04/00413, dated Dec. 27, 2004].